Abstract Background and Aims The underlying mechanism for the increased incidence of chronic kidney disease (CKD) in burn patients discharged from hospital remains unclear. Recent studies have shown that burn patients are discharged from the hospital with chronic inflammation despite normalization of all physiological parameters. We hypothesized that severe burns accelerate the onset and progression of CKD by activating persistent inflammation. This study aimed to investigate the long-term effects of severe burns on kidney and its possible mechanisms. Method The study was divided into three parts. First, to understand the effect of burns on the general population and the CKD population, 4-month-old C57BL/6 mice were divided into a blank control group (Blank) and an adenine-induced CKD group. Some mice were established by burns in a 10% total body burn surface area model at 5-month-old. Experiments were terminated at 7-month-old. The function, morphology, inflammatory response and oxidative stress of the kidney were assayed. Second, the effect of activated macrophages on podocytes was studied by in vitro experiments. Results In the Blank group, burns did not cause kidney function and weight alterations, but caused a small amount of organic lesions, glomerular atrophy, apoptosis, and macrophage infiltration. In the CKD group, burns not only significantly reduced kidney function, but also caused kidney atrophy, organic lesions, glomerular atrophy, apoptosis and macrophage infiltration. In addition, burns significantly increased Caspase-1 and -3 pathway expression in all mice. Electron microscopy showed that burns significantly aggravated glomerular injury in the CKD group, including podocyte injury, cell membrane blubbing and rupture. In vitro studies showed that polarized M1 macrophages increased MPC5 podocytes death. Conclusion Severe burns cause programmed cell death through activation of inflammation-induced Caspase-dependent pathways leading to kidney injury in mice. This phenomenon has a small effect on normal populations and a larger effect on CKD populations. This study has important implications for determining the prognosis of kidney function in burn patients and provides a promising therapeutic strategy.